We will apply micromanipulation techniques routinely used in our laboratory and a fluorometric method scaled down to final volumes in the picoliter range to measure pancreatic secretory proteins (amylase, chymotrypsinogen, trypsinogen, lipase and procarboxypeptidase A) in individual zymogen granules and individual pancreatic exocrine cells. We will evaluate the use of electron probe microanalysis of zinc to determine the distribution of carboxypeptidase among zymogen granules. We will determine if individual cells differ in their qualitative or quantitative responses to secretagogues. Results of this study will clarify the dispute over short-term control versus parallel secretion of pancreatic enzymes. Results of this study will provide for the first time the detailed content of secretory proteins in individual mammalian cells and individual cellular organelles. The methods developed should have wide application in cell physiology.